The cell cycle

or
cell-division cycle
(Interphase & Mitosis)
 Definition:- The cell cycle is the series of events that take place in a cell
leading to DNA replication and cell division that produces two identical
daughter cells.

The cell cycle can be divided in two phases:

a) Interphase (include G1, S and G2 phase);
b) Mitotic phase (M phase) + Cytokinesis.

➢ In cells without a nucleus (prokaryotic), the cell cycle occurs via a process
termed binary fission.
➢ In cells with a nucleus (eukaryotes), the process is termed cell cycle.
 The cell cycle is a vital process
i) by which a single-celled fertilized egg develops into a mature
organism (for development);
ii) by which hair, skin, blood cells, and some internal organs (eg. liver &
kidneys, GI cells) are renewed (need replication).
 S
phase
DNA replication takes
place in the S phase.

G1 G2
interphase

Mitosis
-prophase
-metaphase
-anaphase
-telophase
4
 Cell Cycle: (a) Interphase
i. Interphase proceeds in three phases; G1, S, and G2 phase.
ii. The most significant event is the replication of genetic material
(DNA) in S phase.
ii. During all three phases, the cell grows at G1 phase producing
proteins eg. mRNA and get nutrients; continues to grow as it
duplicates its chromosomes (DNA) at S phase; grows more, take
more nutrients, and prepares for mitosis at G2 phase.
iv. Typically interphase lasts for at least 90% of the total time required
for the cell cycle (long period).
Interphase:- G0 phase or resting phase
• Cells enter the G0 phase from the G1 checkpoint (or Restriction
checkpoint) during the G1 phase.
• This usually occurs in response to a lack of growth factors/nutrients.
G0 phase has two types of cells:- Quiescent cell & Senescent cell
• Quiescent cell (2 types)
(a) Permanent cells:-
• enter the quiescent G0 phase from G1.
• remain quiescent for long periods of time, possibly permanently .
• They are fully differentiated; no need to proliferate; nonproliferative
• But they continue to perform their main functions for the rest of the
organism's life.
eg. neurons
 G0 phase or resting phase (contd)
(b) Some cells enter the G0 phase semipermanentally.
eg. some liver, kidney and muscle cells.
➢ These cells can be induced to begin dividing again only under very
specific circumstances.
• The re-entrant into the cell cycle is possible only by overcoming
the Restriction Point. This is achieved by growth factor-induced
expression of cyclin D proteins. These then overcome the G0
barrier and are able to enter the cell cycle.

(c) Some cells do not enter G0 and continue to divide throughout the
organism's life, e.g. hematopoietic stem cells and gut epithelial cells.
Quiescent cells vs Senescent cells
(i) Quiescent cell is simply a consequence of the cell's lacking any
stimulation to re-enter in the cell cycle.
- Senescent cell is a state that occurs in response to DNA damage
that would make a cell's progeny non-viable.
(ii) Quiescent cell is reversible (re-enter cell cycle);
Senescent cell is irreversible (self-destruction of damaged cell
by apoptosis.)
Interphase: (a) G1 Phase
i. G1 Phase is the first phase of interphase. It is also called the growth
phase. It starts from the end of the previous M phase until the
beginning of DNA synthesis (S phase).
i. During G1 phase, the cell grows in size and synthesizes mRNA and
proteins that are required for DNA synthesis. Once the required
proteins and growth are complete, the cell enters the S phase.
• During this G1 phase, the biosynthetic activities of the cell resume
at a high rate. {The biosynthetic activities of the cell are
considerably slowed down during M phase}
Importance of G1 phase:-
• G1 phase is particularly important in the cell cycle because it
determines whether a cell commits to replicate its DNA or to leave
the cell cycle (G0).
Interphase: (b) S Phase
• In the S phase, DNA replication occurs.
ie. each chromosome has two (sister) chromatids.
The amount of DNA in the cell is double.
Interphase: (c) G2 Phase
• During the G2 phase, the cell continue to grow, accumulates nutrients
needed for mitosis, and prepares for cell division.

• Before a cell can enter cell division (mitosis), it needs to take in

nutrients. All of the preparations are done during interphase.
ie. During the interphase the cell grows (G1), accumulates nutrients
needed for mitosis, and prepares for cell division (G2) and duplicating
its DNA, synthesizing mRNA (S).
Schematic diagram of the cell cycle.
M = Mitosis,
- prophase
- metaphase
- anaphase
- telophase
I = Interphase;
G1 = Gap 1,
S = Synthesis,
G2 = Gap 2,
G0 = Gap 0/Resting.
a) Interphase
(b) Mitosis
b) The term Mitosis is derived from the Greek word μίτος mitos "warp
thread".
c) The mitotic phase is a relatively short period of the cell cycle (10%).

Definition:- Mitosis is the process, in the cell cycle, by which the

chromosomes in the nucleus are divided into two identical sets of
chromosomes, each in its own nucleus.
✓ So, mitosis is the process, in the cell cycle, by which a cell divides
into two genetically identical daughter cells.
Mitosis (M phase, mitotic phase)
• The sequence of events is divided into phases. These phases are
sequentially known as:
(a) Prophase,
(b) Metaphase,
(c) Anaphase,
(d) Telophase
(e) Cytokinesis (strictly speaking, cytokinesis is not part of mitosis but is
an event that directly follows mitosis in which cytoplasm is divided
into two daughter cells)
(a) Prophase
• Prophase comes from the ancient Greek πρό (before) & φάσις
(stage).
• Normally, the genetic material in the nucleus is in a loosely bundled
coil called chromatin. [Chromatin is a complex consisting of both DNA
and specific proteins (histones)]
• At the onset of prophase,
(i) chromatin fibers become tightly coiled, condensing the
chromatin into discrete chromosomes with the condensin complex.
(This process, called chromatin condensation).
(ii) Nuclear membrane starts dissolving.
(iii) Nucleolus starts dissolving.
(iv) Close to the nucleus, two centrosomes appear, consisting of a
pair of centrioles, and actin, a halo of microtubule fragments.
• During prophase, the two centrosomes have increased their
microtubule-activities.
• The centrosomes will be pushed apart to opposite ends of the
nucleus by the action of molecular motors acting on the
microtubules, forming a bridge of spindle fibers (cellular ropes).
• At the end of prophase, the nucleolus disappears.
 Prophase:
(i) The chromatin is
condensing into discrete
chromosomes.
(ii) Nuclear membrane starts
dissolving.
(iii) Nucleolus starts dissolving
(iv) Two centrosomes appear;
consisting of a pair of
centrioles and actin, a halo
of microtubule fragments.
 Late prophase or early metaphase:
(Prometaphase)
(i) The nuclear membrane disintegrates.
(ii) Centrosomes increase their
microtubule-activities.
(a) microtubules have invaded the nuclear
space and attached to kinetochores.
(b) The centrosomes will be pushed apart
to opposite ends of the nucleus by the
action of molecular motors acting on the
microtubules, forming a bridge of spindle
fibers
(iii) At the end of prophase, the nucleolus
disappears.
(b) Metaphase
• Metaphase came from the Greek word μετά (adjacent) and φάσις
(stage).
• Metaphase is a stage of mitosis in which chromosomes align in the
equator of the cell. (before being separated into each of the two
daughter cells)
• Microtubules formed in prophase have already attached
themselves to kinetochores. Then, the two centrosomes start
pulling the chromosomes through their attached centromeres
towards the two ends of the cell. As a result, the chromosomes
come under longitudinal tension from the two ends of the cell.
• To get proper chromosome separation, it is required that every
kinetochore be attached to a bundle of microtubules (spindle fibers).
It is thought that unattached or improperly attached kinetochores
generate a signal to prevent premature progression to anaphase
without all chromosomes being aligned. The signal creates the mitotic
spindle checkpoint (metaphase checkpoint).
• Only after all chromosomes have become aligned at the metaphase
plate, and when every kinetochore is properly attached to a bundle of
microtubules, does the cell enter anaphase.
Metaphase:
The chromosomes align at
the metaphase plate.
Metaphase in cytogenetics and cancer studies
• The analysis of metaphase chromosomes is one of the main tools of
classical cytogenetics and cancer studies.
• Chromosomes are condensed (thickened) and highly coiled in
metaphase, which makes them most suitable for visual analysis.
Metaphase chromosomes make the classical picture of chromosomes
(karyotype).
• For classical cytogenetic analyses, cells are grown in short term
culture and arrested in metaphase using mitotic inhibitor. Further
they are used for slide preparation and banding (staining) of
chromosomes to be visualised under microscope to study structure
and number of chromosomes (karyotype). Staining of the slides, often
with Giemsa (G banding) or Quinacrine, produces a pattern of several
hundred bands.
(c) Anaphase
• from the Greek word ανα meaning "up,“ "against," "back," or "re-").
• When every kinetochore is attached to each of microtubules and the
chromosomes have lined up along the metaphase plate, the cell
proceeds to anaphase.
• In anaphase, two events occur;
• (i) The proteins that bind sister chromatids together are cleaved.
These sister chromatids now become separate daughter chromosome
• (ii) Each daughter chromosomes are pulled apart by shortening
kinetochore microtubules and move toward the respective
centrosomes to which they are attached. The cleaved centromeres go
first while the chromatids trail behind. They all look like a V shape.
• At the end of anaphase the kinetochore microtubules all degrade.
Anaphase:
(i) The chromosomes split
(ii) The kinetochore
microtubules shorten.
Image of the mitotic spindle in
a human cell showing
microtubules in green,
chromosomes (DNA) in blue,
and kinetochores in red.
 (d) Telophase
• Telophase derived from the Greek word τελος meaning "end“.
i. At telophase, the corresponding daughter chromosomes attach at
opposite ends of the cell.
ii. A new nuclear membrane is formed around each set of separated
daughter chromosomes, and
ii. The nucleolus reappears.
• Both sets of chromosomes (with new nucleolus) begin to "relax" or
decondense back into chromatin.
• Mitosis is complete, but cell division is not.
cleavage furrow Telophase:
The decondensing
chromosomes are
surrounded by nuclear
membranes. Cytokinesis
has already begun; the
pinched area is known as
the cleavage furrow.
(e) Cytokinesis
• Cytokinesis is often mistakenly thought to be the final part of
telophase; however, cytokinesis is a separate process that begins at
the completion of telophase.
• Cytokinesis is necessary for completing cell division. As mitosis
completes (completion of telophase), the cell begins cytokinesis.
• In animal cells, the cell pinches inward at the cleavage furrow,
separating the two developing nuclei. Eventually, the parent cell will
be split in half, giving rise to two daughter cells, each with a
replication of the original genome.
• Each daughter cell has a complete copy of the genome of its parent
cell.
• The end of cytokinesis marks the end of the M-phase.
• In general, mitosis is followed immediately by
• cytokinesis, which divides the cytoplasm, organelles, nucleus and
cell membrane into two.
• Thus dividing the cell into two new cells containing equal shares of
these cellular components.
• Mitosis and cytokinesis together define the mitotic (M) phase of the
cell cycle.
Overview of mitosis process:-
• Mitosis begins when the chromosomes condense and become visible (prophase)
• The nuclear membrane disintegrates into membrane vesicles. The nucleolus also dissolves.
Two centrosomes appear.
• The chromosomes align themselves in a line spanning the cell (metaphase).
• Microtubules splay out from opposite ends of the cell and shorten, pulling apart the sister
chromatids of each chromosome. Sister chromatids at this point are called daughter
chromosomes.
• As the cell elongates, corresponding daughter chromosomes are pulled toward opposite
ends.
• A new nuclear membrane forms around the separated daughter chromosomes.
• As mitosis completes, the cell begins cytokinesis.
• In animal cells, the cell pinches inward at the imaginary line (the area of the cell membrane
that pinches to form the two daughter cells is called the cleavage furrow), separating the two
developing nuclei.
• Eventually, the parent cell will be split in half, giving rise to two daughter cells, each with a
replica of the original genome
Overview of cell cycle in relation to mitosis
• The primary result of mitosis is the transferring of the parent cell's
genome into two daughter cells. These two daughter cells are
identical.
• Because each resultant daughter cell should be genetically identical
to the parent cell, the parent cell must make a copy of each
chromatid before mitosis. This occurs during the S phase of
interphase. The two identical chromatids resulting from chromatid
duplication are called sister chromatids. They are held together by a
specialized region of the chromosome: a DNA sequence called the
centromere.
Cell cycle (overview):-
Major events in mitosis (overview)
Mitosis divides the chromosomes in a cell nucleus.
Significance of mitosis
• Mitosis is important for the maintenance of the chromosomal set.
• After mitosis, each cell receives chromosomes that are same in
composition and equal in number to the chromosomes of the parent
cell.

Errors in mitosis can either

(a) kill a cell through apoptosis or
(b) cause mutation. Certain types of cancer can arise from such
mutation
Mitosis occurs in the following circumstances:
(a) Development and growth
• The number of cells within an organism increases by mitosis. This is
the basis of the development of a multicellular body from a single
cell, ie. zygote and also the basis of the growth of a multicellular
body.
(b) Cell replacement
• In some parts of body, eg. skin and digestive tract, cells are constantly
sloughed off and replaced by new ones. New cells are formed by
mitosis and so are exact copies of the cells being replaced.
Consequences of errors
• In nondisjunction, a chromosome may fail to separate during
anaphase. So, one daughter cell will receive both sister chromosomes
and the other will receive none.
• The daughter cell who received both sister chromosomes, if fertilize
with normal cell, will result in Trisomy (two sisters chromosome and a
homologue chromosome; having three chromosomes).
• The daughter cell who received none chromosome, if fertilize with
normal cell, will result in monosomy; [having only one chromosome
(the homologous chromosome)].
• These cells are considered aneuploid, a condition often associated
with cancer.
Schematic diagram of the cell cycle
M = Mitosis,
- prophase
- metaphase
- anaphase
- telophase
I = Interphase;
G1 = Gap 1,
S = Synthesis,
G2 = Gap 2,
G0 = Gap 0/Resting.
Three types
of
cell division
3. Molecular analysis is performed on the three copies of chromosome 21 in
a child with Down syndrome using DNA polymorphisms for which both
parents are heterozygous for different alleles. Two of the chromosomes in
the child contain the same alleles as one of the mother's alleles. Based on
this, when did the nondisjunction event most likely occur?
A Maternal meiosis I
B Maternal meiosis II
C Paternal meiosis I
D Paternal meiosis II
E Cannot be determined with the data provided
The correct answer is B. This pattern indicates that the nondisjunction
occurred in the mother in the second meiotic division, when the two
chromatids would be identical. First-division nondisjunction would result in
the child having each of the mother's two alleles and one of the father's.
 State Description Function
Quiescent/ Gap 0 A resting phase where the cell has left the cycle and has
Senescent (G0) stopped dividing.
Gap 1 Cells increase in size in Gap 1 (grow). The G1 checkpoint control
(G1) mechanism ensures that everything is ready for DNA synthesis.

Synthesis DNA replication occurs during this phase.

Interphase (S)
The cell will continue to grow. The G2 checkpoint control
Gap 2 mechanism ensures that everything is ready to enter the M
(G2) (mitosis) phase and divide.

Cell growth stops at this stage and cellular energy is focused on

Cell Mitosis the orderly division into two daughter cells. A checkpoint in the
division middle of mitosis (Metaphase Checkpoint) ensures that the cell
(M)
is ready to complete cell division
Regulation of cell cycle
Two types:
(i) Regulation by Cyclins and CDKs (Cyclin-dependant kinases);
(ii) Regulation by Checkpoints of cell cycle

Regulation of the cell cycle is crucial to the survival of a cell, including

(a) the detection and repair of DNA damage as well as
(b) the prevention of uncontrolled cell division.